Acute and chronic diseases of the lungs affect one of the broadest patient populations and represent some of the most urgent and unmet health care needs. Acute illnesses of the lungs include neonatal conditions related to incompletely developed lungs, severe infections, burns and other lung injuries, and Acute Respiratory Distress Syndrome (ARDS). These conditions are often treated using mechanical ventilation to sustain patient oxygen levels while the lungs recover. In intensive-care and emergency settings, oxygenation is often accomplished by ventilation. However, this method requires functioning lungs and often results in mechanical trauma or infection.
Chronic diseases of the lungs include chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), mesothelioma, and lung cancer. Chronic insufficient oxygenation is typically treated using portable oxygen therapy, which still depends on oxygen transfer to the blood stream across diseased or damaged lungs, and does not address the underlying condition. Pharmacologic therapies are also used, but have limited effectiveness.
Since portable oxygen therapy, mechanical ventilation, and similar approaches generally require functioning lungs to achieve oxygenation and carbon dioxide removal, patients with damaged or diseased lungs are often barely sustained by these methods. In the typical course of events, patients have severe limits of exertion placed upon them, since their oxygen levels are insufficient even for sustaining resting requirements. As the patients' lungs continue to fail, limits on their activity and their overall health become more severe, with many acute exacerbations and hospitalizations and a steadily worsening prognosis.
More advanced treatments for lung failure have been developed over the past few decades. Currently, patients suffering from cardiac and pulmonary failure may be treated with a therapy known as extracorporeal membrane oxygenation (ECMO), which effectively bypasses the lungs. ECMO is used frequently in neonates and children. ECMO technology exists in several configurations, including hollow fiber-based systems, planar or flat sheet configurations, and spiral or wound systems. Typically, these devices include an oxygenator as the central component of the system, along with heat exchangers, bubble traps, fluid circuitry, pumps, and other components.
In ECMO, blood is typically pumped from the internal jugular vein through an oxygenation device, and back into the carotid artery. (In an alternative to this venous-arterial circuit, a veno-venous circuit may also be used, depending on the needs of the patient.) More particularly, in typical devices, blood is drained from the venous supply into a reservoir, or bladder, and the tubing, typically made from materials such as PVC or Tygon, leads to the actual ECMO pump (often a roller pump). The pump, in turn, drives the blood through a membrane oxygenator, which transfers oxygen into the blood and removes carbon dioxide across the membrane. In one implementation, the membrane oxygenator is formed by a flat, thin silicone-rubber membrane stretched across a plastic frame, and is often rolled into a cylinder. The pumping process typically results in a lowering of the blood temperature, and, therefore, a heat exchanger is often used to maintain body temperature. The blood pressure is carefully monitored in this system, as are the oxygen and CO2 levels in the blood. Detection of bubbles, in order to prevent an air embolism, is another generally important element of the system. In order to avoid clotting, large doses of anti-coagulants such as heparin may be provided.
In one common, fiber-based oxygenation configuration, blood is channeled outside hollow fibers of a fiber bundle, while oxygen is passed through the lumens of the fibers. Generally, the fibers are porous, and therefore some plasma leakage occurs, but blood proteins quickly block significant leakage through a combination of physical and surface energy mechanisms. In some instances, the fibers are coated with a film of silicone to prevent plasma leakage. One older technology utilizes flat sheet membranes stacked in a planar configuration. Limitations on conventional fabrication technologies for such devices severely limit the device performance. For instance, limitations on the membrane thickness, channel depth, width of spacers between parallel channels, and flow paths in the manifold collectively limit the ability to miniaturize and inexpensively manufacture systems with high gas transfer rates.
The non-physiologic nature of the ECMO circuit also imposes certain disadvantages. Because blood is oxygenated through a large compartment, fluid forces acting on the blood differ substantially from those in alveolar capillaries. These differences can lead to inflammatory responses that increase morbidity and mortality in ECMO, both in neonatal and pediatric populations. In addition, anomalous flow paths and contact between blood and artificial materials such as PVC, Tygon, and silicone rubber can cause a high incidence of clotting, unless large doses of anticoagulants are supplied. These anticoagulants, such as heparin, can lead to complications such as excessive bleeding and electrolyte-related imbalances. The deleterious blood surface interactions that lead to coagulation in artificial organ assist device systems can be reduced by selecting materials with high hemocompatibility, but adverse interactions are often unavoidable. Therefore, reduced surface areas are highly desired.
In addition to therapeutic applications for treatment of disease, cardiopulmonary support is typically required for surgical procedures such as Coronary Artery Bypass Graft (CABG), where the patient is placed on a bypass pump circuit that oxygenates the blood during the operation. Over 500,000 of these operations are done annually in the United States alone. Current membrane oxygenator technology for CABG procedures generally require very large prime volumes of blood in the device (i.e., large blood volumes to fill the device) and significant anticoagulation, and typically include complex circuitry that necessitates highly trained perfusionists to operate. Large prime volumes result, for example, from limitations in the smallest diameter or other critical dimensions of hollow fibers or flat sheet systems. They often lead to a need for blood transfusions and for a large percentage of the patient's blood to be outside the body at any given time during the treatment. Conventional ECMO devices typically also require a large surface area. The surface area is driven by the requirement for sufficient oxygen and carbon dioxide transfer rates, and sufficiently high rates generally require very large surface area, in particular if the gas transfer membrane is thick. Larger surface areas, in turn, lead to larger systems, more expensive material costs, and more extensive problems with blood-surface interactions.
Accordingly, there is a need for improved ECMO devices that facilitate high oxygen transfer rates with smaller prime volumes and surface areas, and that are less prone to coagulation and inflammation. The present invention addresses this need and provides other related advantages.